Drugs: aminoglycosides Flashcards
solubility of aminoglycosides
highly water soluble agents so limited ability to cross lipid bilayer
what is gentamicin?
aminoglycoside
- boras spectrum of action
generally uesd to treat grma negative bacteria, gram pos staphylococci and gram positive myoplasma
what is Tobramycin
clincially interchangable with gentamicin
- mainly used topically to treat bacteria that are resistant to gentamicin
- more expensive tho
what is amikacin
resistant to most aminoglycoside-modifying enzymes
used systemicaly to treat bacteria that are resistant to gentamicin
what binds and inhibts 50S subunit of ribosome
acrolides, chloramphenicol, lincosamides, streptogramins, oxazolidinones, and pleuromutilins
What binds and inhibits the 30S subunit of the ribosome
Aminoglycosides, spectinomycin, and tetracyclines bind to and inhibit the activity of 16S rRNA in the 30S subunit
what are tetracyclins
derived from streptomyces bacteria or produced semi synthetic derivates of tetracycline (oxytetracycline)
- considered to have a braod spectrum of activity but mainly used to treat infections caused by atypical bacteria (neither gram pos or gram neg)
MOA tetracyclins
- bind 30S subunit of bacterial ribsomse (same as aminoglycosides) to inhibit proten synthesis
- do this by prevening the binding of aminoacyl-tRNA through allosterically binding to the ribosome
- binding is reversible (unlike aminoglycosides) and voerall effect is bacteriostatic not bacteriocidal
what bacteria do tetracyclins treat
- activity against gram pos and gram neg aerobes and anerobes but used to treat atypical like rickettsia, chamydia and mycoplasmab
^drug of choice in thsoe situations
- also have activity against some protozoa and effective but slow acting anti-malarial
what antimicrobial drugs target teh #) s ribosomal subunit
- streptomycin and gentamicin (aminoglycosides_
Spectinomycin is a structural relative of the aminoglycosides.
Tetracycline and doxycycline are tetracyclines. Tigecycline is a glycylcycline.
doxcyline in acne treatment
has anti MMP and ROS scavening properties but also inhibits phospholipase AS
- used to reat rosacea and acne which are inflammatory skin condiitons
what are glycylcylines
new class of antibiotcs that are derived from tetracyclines
- Tigecycline is first made vaialble, its based on modification of minocycline that gives it a 5x greater affinity for ribosomal binding allowing it to overcome ribosomal protection
- has large side chain which may inhibit from permeating the efflux pump
- bactteriostatic and broad spec including gram pos, gram neg and anerobic bacteria that are resistant to other drugs
what is TMS
aka co-trimoxazole, combo of sulfonamides (S) and trimethoprim (TM) referred to as potentiated sulfonamide (TM + S)
effect is often bactericidal
*sulfonamides are ineffective when used alone
what are sulfonamides
aka sulfa drugs, antimicobial agents that contain a sulfonamide group
- inhibit the metabolic pathway required for folic acid synthesis
- sulfonamides are competitive inhbitors of dihydropteroate synthetase - key enzyme in folate synthesis
*alone sulfonammides are bacteriostatic, and not v effective
adverse effects of sulfonamides
May be mild or erious
Fiver and skin problems, esp if drug is aplpied topically
Allergies common to oral preps
Precipitation of drug and metabolites in renal tubules of dehydrates patietns may occur and cause renal damage
Kernicterus: rare, displcaemnt of bilirubin from albumin in infants which then crosses the BB. Regions most commonly affected are basal gnaglia, hippocampus and geniculate bodies which cause various signs of brain damage
what is ciprofloxacin
Type of fluoroquinolone
Activity spec is similar to gentamycin
can target many Gram negative aerobes but Staphylococcus are essentially the only Gram positive that it will have activity against
used to treat mycoplasma and chlamydia but ciprofloxacin is ineffective against all anaerobes.
what are macrolides
Target the 50S ribosomal subunit
Have large lactone ring attached to one or more deoxy sugars
Activity on some atypical bacteria
Mainly bacteriostatic
One of safest antibacterials
pharmacokinetics of macrolides
Metabolized and excreted in bile, but erythromycin shown to inhibit P450 metabolism of other drugs - consider before prescribing other meds
Widely distribute except the CNS, one of few antimicrobials that enters prostate relatively well
Also dsitributes well to lungs and concnetrate in lung (can be 100x higher than in plasma)
adverse effects of macrolides
Tissue irritation (severe pain with IM admin and vomiting
Vomiting esp problematic with erythromycin
MOA of macrolides
Inhibiiton of proien synthesis by binding reversibly to bacterial ribosmoes 50S subunit
causing dissociation of peptide carrying tRNA from ribosome during translocation
what is Erythromycin
Most common macrolide similar spectru to amoxicillin
shown to inhibit P450 metabolism of other drugs - consider before prescribing other meds
Major vomiting side effect bc stimulates motilin receptors in GI tract causing nausea (highly variable between aptients)
Azithromycin
Newer macrolide that’s more effectie than erythromycin against gram neg aerobes
Logner half life and can be administered once daily rather than 4 times a day
Commonly used for resp tract infections and one of worlds best selling drugs
clarithromycin
Newer macrolie
More effective than erythromycin and azithromycin against gram positive apthogens
Logne rhalf life than erythromycin and therefore needs to be admin twice a day
Common to treat community acquired respiratory tract infections
More acid stable than erythromycin so has fewer GI adverse effects
what is telithromycin?
Treatment of certant resistant respiratory pathogens
Resistance that develops following administration of macrolides is mainly due to target modification and efflux pumps
macrolides are predominantly prescribed as antimicrobial agents, they also have anti-inflammatory effects that inhibit neutrophil migration and leukotriene synthesis.
what is Chloramphenicol
Also targets 50S subunit
Isolated from Streptomyces venezuelae
bacteriostati active against both aerobic and anaerobic Gram positive and Gram negative organisms.
Penetrates the cornea really well
Available on oral, topical and injectible forms
Currently banned in good producing animals due to documented fatailied
Only use in those with serious infections when less potentially dangerous drugs are ineeffective or contraindicted
adverse effects of chloramphenicol
Usually very safe but fatal aplastic anemia can occur in humans
Only in 1/30,000 and due to genetic defect that is simialr to malignan hyperthermia
Effect not dose related or irreversible and may occur weeks ro months after therapy is stopped
